Systems and methods for automated preparation of biological specimens

ABSTRACT

An automated system for processing a sample contained in a liquid sample container includes an automated tool head configured to rotate about a first axis, and to translate along a second axis different than the first axis, an analytic element positioner having an analytic element holder configured to releasably grip an analytic element, and a specimen transfer device carried by the tool head, wherein the tool head is configured to automatically position a working end of the specimen transfer device to obtain a specimen from a sample container held in the sample container holder, and to transfer the obtained specimen to an analytic element held by the analytic element holder, respectively, through one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis.

RELATED APPLICATIONS DATA

The present application is a National Phase entry under 35 U.S.C § 371of International Patent Application No. PCT/US2018/021879, filed Mar. 9,2018, which claims priority to U.S. patent application Ser. No.15/454,819, filed Mar. 9, 2017, now abandoned, the contents of which areincorporated by reference in their entirety into the presentapplication.

FIELD

The present disclosure generally relates to preparation of biologicalspecimens, and more particularly, to automated systems and methods forcollecting a biological specimen from a liquid sample container anddispensing the specimen onto an analytic element, such as a specimenslide, as well as automated systems and methods for obtaining an aliquotof the sample for additional testing.

BACKGROUND

Cytology is a branch of biology dealing with the study of the formation,structure, and function of cells. As applied in a laboratory setting,cytologists, cytotechnologists, and other medical professionals makemedical diagnoses of a patient's condition based on visual examinationof a specimen of the patient's cells. A typical cytological technique isa “pap smear” test, in which cells are scraped from a woman's cervix andanalyzed in order to detect the presence of abnormal cells, a precursorto the onset of cervical cancer. Cytological techniques are also used todetect abnormal cells and disease in other parts of the human body.

Cytological techniques are widely employed because collection of cellsamples for analysis is generally less invasive than traditionalsurgical pathological procedures such as biopsies, whereby a solidtissue specimen is excised from the patient using specialized biopsyneedles having spring loaded translatable stylets, fixed cannulae, andthe like. Cell samples may be obtained from the patient by a variety oftechniques including, for example, by scraping or swabbing an area, orby using a needle to aspirate body liquids from the chest cavity,bladder, spinal canal, or other appropriate area. The acquired cellsample is typically placed in a preservative solution and subsequentlyextracted from the solution and transferred to a glass slide. A fixativeis applied to the cell sample to ensure the cells remain in place on theglass slide for facilitating subsequent staining and examination.

It is generally desirable that the cells on the slide have a properspatial distribution, so that individual cells can be examined. A singlelayer of cells is typically preferred. Accordingly, preparing a specimenfrom a liquid sample containing many cells (e.g., tens of thousands)typically requires that the cells first be separated from each other bymechanical dispersion, liquidic shear, or other techniques so that athin, monolayer of cells can be collected and deposited on the slide. Inthis manner, the cytotechnologist can more readily discern the presenceof any abnormal cells in the patient sample. The cells are also able tobe counted to ensure that an adequate number of cells have beenevaluated.

Certain methods and apparatus for generating a thin monolayer of cellsand from a liquid sample container and then transferring this thin layerto a “specimen slide” that is advantageous for visual examination aredisclosed in U.S. Pat. Nos. 5,143,627, 5,240,606, 5,269,918, 5,282,978,6,562,299, 6,572,824 and 7,579,190, the disclosures of which areincorporated herein by reference in their entirety. According to onemethod disclosed in these patents, a patient's cells in a preservativeliquid in a sample container are dispersed using a spinning samplecollector disposed therein. A controlled vacuum is applied to the samplecollector to draw the liquid through a screen filter thereof until adesired quantity and spatial distribution of cells is collected againstthe filter. Thereafter, the sample collector is removed from the samplecontainer and the filter portion impressed against a glass slide totransfer the collected cells to the slide in substantially the samespatial distribution as collected. Apparatus manufactured according tothe teachings of one or more of these patents have been commerciallysuccessful, such as the ThinPrep® 2000 Processor (specimen slidesprocessed from patient samples one at a time), and the ThinPrep® 5000Processor (specimen slides batch processed from patient samples), whichare manufactured and sold by Hologic, Inc., located in Marlborough,Mass. Further reference is made to U.S. Pat. Nos. 7,556,777, and7,771,662, the disclosures of which are incorporated herein by referencein their entirety.

Once a specimen slide has been prepared, the specimen may be visuallyinspected by a cytotechnologist, typically under magnification, and withor without various sources of illumination. Additionally, oralternatively, automated slide imaging systems are used to aid in thecytological inspection process. For example, an automated slide imagingsystem may capture an image of all, or substantially all, of the cellscaptured on the slide, and perform a preliminary assessment of the cellsusing image processing techniques in order to direct thecytotechnologist to potentially the most relevant cells on the slide forclose inspection. Examples of such imaging systems are disclosed in U.S.Pat. Nos. 7,587,078, 6,665,060, 7,006,674 and 7,590,492, the disclosuresof which are incorporated herein by reference in their entirety. Whetherby inspection of the actual specimen slide under magnification, or ofmagnified images of the specimen, the specimen is typically classifiedby the cytotechnologist as either “normal” or “abnormal,” wherein anabnormal sample normally falls in one of the major categories defined byThe Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnosis,which categories include Low-Grade Squamous Intraepithelial Lesions(LSIL), High-Grade Squamous Intraepithelial Lesions (HSIL), SquamousCell Carcinoma, Adenocarcinoma, Atypical Glandular cells of UndeterminedSignificance (AGUS), Adenocarcinoma in situ (AIS), and Atypical SquamousCell (ASC). Additional information regarding cell specimenclassifications is widely available.

It may be desirable to perform other types of diagnostic testing of thesame patient sample, such as for Human Papilloma Virus (HPV). Based onthe strong correlation between HPV and cervical cancer, it has beenrecommended that HPV DNA testing be used as a triage test for patientswhose Pap smear results are classified as ASC-US. In the case where aliquid-based Pap smear has been performed, the same sample used toperform the Pap smear analysis can be conveniently used to perform a“reflexive” HPV DNA test, thereby obviating the need for a repeat clinicvisit and second Pap smear. For example, if a specimen is classified aspositive for ASC-US, an “aliquot” (e.g., 4 mL) of the liquid sample maybe removed from the stored vial and sent to a molecular diagnosticlaboratory for HPV DNA testing.

Significantly, laboratories that perform HPV DNA tests are weary ofmolecular contamination, a well-known problem in molecular diagnosticlaboratories. Thus, due to the risk of cross-contamination, moleculardiagnostic laboratories may not accept aliquots that have been takenfrom an already processed liquid-based Pap smear for fear ofunnecessarily generating false HPV positives. As such, it is desirableto obtain and store an aliquot of each patient sample prior to thespecimen slide making process in order to preserve a portion of thesample without exposure to cross-contamination. By way of example,certain methods and apparatus for obtaining an aliquot of a patientsample prior to the specimen slide making process are disclosed in U.S.Pat. Nos. 7,674,434, and 8,137,289, the disclosures of which areincorporated herein by reference in their entirety. Additional examplesof obtaining sample aliquots in general but not necessarily inconjunction with making specimen slides are disclosed in U.S. Pat. No.9,335,336 and U.S. Pat. Publ. No. 2017/0052205, the disclosures of whichare incorporated herein by reference in their entirety.

Besides being used for HPV DNA testing, aliquots from liquid-based Papsmear samples can also be used DNA testing for other sexuallytransmitted diseases, such as Chlamydia trachomatis and Neisseriagonorrhoeae. However, false positives are a special problem when testingfor Chlamydia trachomatis and Neisseria gonorrhoeae, because they couldhave enormous family and social repercussions. Thus, moleculardiagnostic laboratories are even more reluctant to accept aliquots fromalready processed liquid-based Pap smear samples. Testing for othersexually transmitted diseases need not be used only to triage ASC-USspecimens. Indeed, such testing is intended to be performed in parallelto the Pap smear tests at the request of the physician, aliquots may betaken from the Pap smear samples prior to processing, e.g., by manuallypipetting the aliquot from the vial, thereby minimizing the risk ofcross-contamination. However, this step may still not satisfy the strictcontamination prevention requirements imposed by molecular diagnosticlaboratories.

In addition to contamination issues, the pipetting of an aliquot from aliquid-based Pap smear sample, whether done before or after the sampleis processed, and whether done for HPV testing or testing of any othersexually transmitted disease, increases cost in the form of manual laborwhich involves not only pipetting the aliquot into an extra vial, butalso labeling the vial.

There thus is a need to provide improved apparatus and methods forobtaining an aliquot from a liquid-based biological sample, such as aPap smear sample while minimizing the risk of cross-contamination.

SUMMARY

Embodiments of the present disclosure are directed to improved automatedsystems and methods for processing a sample (such as a biologicalsample) contained in a sample container.

In one embodiment, an automated system for processing a sample containedin a liquid sample container includes a sample container holderconfigured for holding a sample container and an automated tool headconfigured to rotate about a first axis, and to translate along a secondaxis different than the first axis, the system further including aspecimen transfer device carried by the tool head, wherein the tool headis configured to automatically position a working end of the specimentransfer device to obtain a specimen from a sample container held in thesample container holder, and then to transfer the obtained specimen toan analytic element (e.g., a slide) held in an analytic element holder,respectively, through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis.Without limitation, the working end of the specimen transfer device maybe configured to receive a filter thereon, the filter comprising atubular body that forms a seal with the working end portion of thespecimen transfer device and a porous membrane end portion that isconfigured to allow liquid to pass therethrough while retaining cellularmatter on an outer surface thereof.

The system may further include an analytic element positioner includingthe analytic element holder, wherein the analytic element holder isconfigured to releasably grip the analytic element. The analytic elementpositioner may be configured to automatically place an analytic elementcarried by the analytic element positioner into a fixative containerheld in the fixative container holder after a specimen has beentransferred onto the analytic element. The system may include ananalytic element (e.g., slide) loading platform located on a surface ofthe tool head, wherein the analytic element positioner operativelycooperates with the tool head so that the analytic element holderautomatically engages and removes an analytic element placed on theloading platform, and wherein the analytic element positioneroperatively cooperates with the tool head to automatically position anengaged analytic element proximate the working end of the specimentransfer device to transfer the specimen onto the engaged analyticelement.

The system may further include a sample container capping devicedisposed on the tool head and configured to controllably grip andrelease a cap of a sample container held in the sample container holder,wherein the tool head is configured to automatically position the samplecontainer capping device proximate the sample container cap through oneor both of rotation of the tool head about the first axis andtranslation of the tool head along the second axis, and wherein thesample container capping device operatively cooperates with the samplecontainer holder to remove or install the sample container cap. Withoutlimitation, the sample container holder may be configured toautomatically rotate in one of a clockwise rotational direction and acounter-clockwise rotational direction while the sample containercapping device engages the sample container cap in order to remove thesample container cap from the sample container, and wherein the samplecontainer holder is configured to automatically rotate in the other oneof the clockwise rotational direction and the counter-clockwiserotational direction while the sample container capping device engagesthe sample container cap in order to install the sample container caponto the sample container.

The system may further include a pipette tip dispenser and a pipettorcarried by the tool head, the pipettor having a pipette tip engagingmember configured to releasably engage pipette tips, wherein the toolhead is configured to automatically position the pipette tip engagingmember proximate the pipette tip dispenser to allow the pipette tipengaging member to engage a pipette tip held by the pipette tipdispenser through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis.Without limitation, the pipette tip dispenser may be mounted on apipette tip dispenser transporter configured to translate the pipettetip dispenser relative to the tool head so that the pipette tipdispenser may be selectively translated to a location at which the toolhead positions the pipette tip engaging member to engage a pipette tipfrom the pipette tip dispenser. The system may further include a pipettetip dispenser isolation chamber, wherein the pipette tip dispensertransporter is configured to selectively translate the pipette tipdispenser between the location at which the tool head positions thepipette tip engaging member to engage a pipette tip from the pipette tipdispenser and a second location within the isolation chamber. A pipettetip waste bin may be mounted on the pipette tip dispenser transporter,wherein the pipette tip dispenser transporter is configured toselectively translate the pipette tip waste bin to a location at whichthe tool head positions the pipette tip engaging member to disengage apipette tip into the pipette tip waste bin. For example, the pipette tipwaste bin may be mounted on the pipette tip transporter relative to thepipette tip dispenser such that, when the pipette tip waste bin istranslated to the location at which the tool head positions the pipettetip engaging member to disengage a pipette tip into the pipette tipwaste bin, the pipette tip dispenser is simultaneously translated intothe isolation chamber.

In embodiments including the pipettor, the system may further include asupplemental container holder configured for holding a supplementalcontainer, wherein the tool head is configured to automatically positionthe pipette tip engaging member into a position in which a pipette tipengaged on the pipette tip engaging member is inserted into a samplecontainer held in the sample container holder, and into a position inwhich the engaged pipette tip is inserted into a supplemental containerheld in the supplemental container holder, respectively, through one orboth of rotation of the tool head about the first axis and translationof the tool head along the second axis. The supplemental container maybe an aliquot container, wherein when the tool head and pipettoroperatively cooperate to automatically cause the pipette tip engagingmember to engage a pipette tip from the pipette tip dispenser, draw analiquot of a sample from a sample container held in the sample containerholder using the engaged pipette tip, and dispense the obtained samplealiquot into the aliquot container, respectively. Alternatively, andwithout limitation, the supplemental container may be a reagentcontainer containing a reagent, and wherein when the tool head andpipettor operatively cooperate to automatically cause the pipette tipengaging member to engage a pipette tip from the pipette tip dispenser,draw an aliquot of reagent from the reagent container using the engagedpipette tip, and dispense the reagent aliquot into a sample containerheld in the sample container holder, respectively.

A supplemental container capping device may be disposed on the tool headand configured to controllably grip and release a cap of a supplementalcontainer held in the supplemental container holder, wherein the toolhead is configured to automatically position the supplement containercapping device proximate the supplemental container cap through one orboth of rotation of the tool head about the first axis and translationof the tool head along the second axis, and wherein the supplementcontainer capping device operatively cooperates with the supplementalcontainer holder to remove or install the supplemental container cap.For example, the supplemental container holder may be configured toautomatically rotate in one of a clockwise rotational direction and acounter-clockwise rotational direction while the supplement containercapping device engages the supplemental container cap in order to removethe supplemental container cap from the supplemental container, andwherein the supplemental container holder is configured to automaticallyrotate in the other one of the clockwise rotational direction and thecounter-clockwise rotational direction while the supplement containercapping device engages the supplemental container cap in order toinstall the supplemental container cap onto the supplemental container.In some embodiments including both a sample container capping device anda supplemental container capping device, the two capping devices may beoffset from one another on the tool head such that, when the samplecontainer capping device is in a position to grip and remove the samplecontainer cap, the supplemental container capping device is in aposition to grip and remove the supplemental container cap withoutfurther rotational movement of the head tool.

The system may further include an analytic element (e.g., slide) loadingplatform located on a surface of the tool head, wherein the analyticelement positioner operatively cooperates with the tool head so that theanalytic element holder automatically engages and removes an analyticelement placed on the loading platform, and wherein the analytic elementpositioner operatively cooperates with the tool head to automaticallyposition an engaged analytic element proximate the working end of thespecimen transfer device to transfer the specimen onto the engagedanalytic element.

The system may further include a reader (e.g., a bar code reader orscanner) positioned on the tool head and configured for reading samplecontainer indicia located any of a sample container. An analytic elementprinter may be provided in communication with reader and configured forprinting analytic element indicia corresponding to sample containerindicia read by the reader onto an analytic element, which may be,without limitation, a slide. An aliquot container printer may also beprovided in communication with the reader and configured for printinganalytic element indicia corresponding to sample container indicia readby the reader onto an aliquot container. In various embodiments, thereader is further configured to read indicia on other system componentsand consumables, such as on a slide or on a filter used for obtaining asample specimen.

Embodiments of the system may include a controller for controllingoperation of one or more of the tool head, pipettor, capping devices,and analytic element positioner, as well as a user interface operativelycoupled with the controller and configured for displaying system statusand/or inquires to a system operator, and for receiving user inputs inresponse to the displayed system status and/or inquires.

In one embodiment, an automated system for processing a sample containedin a liquid sample container includes a sample container holderconfigured for holding a sample container, an automated tool headconfigured to rotate about a first axis, and to translate along a secondaxis different than the first axis, a pipette tip dispenser, a pipettorcarried by the tool head, the pipettor having a pipette tip engagingmember configured to releasably engage pipette tips, wherein the toolhead is configured to automatically position the pipette tip engagingmember proximate the pipette tip dispenser to allow the pipette tipengaging member to engage a pipette tip held by the pipette tipdispenser through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis,wherein the pipette tip dispenser is mounted on a pipette tip dispensertransporter configured to translate the pipette tip dispenser relativeto the tool head so that the pipette tip dispenser may be selectivelytranslated to a location at which the tool head positions the pipettetip engaging member to engage a pipette tip from the pipette tipdispenser; and a pipette tip dispenser isolation chamber, wherein thepipette tip dispenser transporter is configured to selectively translatethe pipette tip dispenser between the location at which the tool headpositions the pipette tip engaging member to engage a pipette tip fromthe pipette tip dispenser and a second location within the isolationchamber.

In yet another embodiment, an automated system for processing a samplecontained in a liquid sample container includes sample container holderconfigured for holding a sample container, an automated tool headconfigured to rotate about a first axis, and to translate along a secondaxis different than the first axis, a pipette tip dispenser, a pipettorcarried by the tool head, the pipettor having a pipette tip engagingmember configured to releasably engage pipette tips, wherein the toolhead is configured to automatically position the pipette tip engagingmember proximate the pipette tip dispenser to allow the pipette tipengaging member to engage a pipette tip held by the pipette tipdispenser through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis, and asupplemental container holder configured for holding a supplementalcontainer, wherein the tool head is configured to automatically positionthe pipette tip engaging member into a position in which an engagedpipette tip is inserted into a sample container held in the samplecontainer holder, and into a position in which an engaged pipette tip isinserted into a supplemental container held in the supplementalcontainer holder, respectively, through one or both of rotation of thetool head about the first axis and translation of the tool head alongthe second axis. Without limitation, the supplemental container may beone of a reagent container and an aliquot container.

In still another embodiment, a system for processing a sample containedin a liquid sample container includes a sample container holderconfigured for holding a sample container, a supplemental containerholder configured for holding a supplement container, an automated toolhead configured to rotate about a first axis, and to translate along asecond axis different than the first axis, a first capping devicedisposed on the tool head and configured to controllably grip andrelease a cap of a sample container held in the sample container holder,wherein the tool head is configured to automatically position the firstcapping device proximate the sample container cap through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis, and wherein the first capping deviceoperatively cooperates with the sample container holder to remove orinstall the sample container cap, and a second capping device disposedon the tool head and configured to controllably grip and release a capof a supplemental container held in the supplemental container holder,wherein the tool head is configured to automatically position the secondcapping device proximate the supplemental container cap through one orboth of rotation of the tool head about the first axis and translationof the tool head along the second axis, and wherein the second cappingdevice operatively cooperates with the supplemental container holder toremove or install the supplemental container cap. The sample containerholder may be configured to automatically rotate in one of a clockwiserotational direction and a counter-clockwise rotational direction whilethe first capping device engages the sample container cap in order toremove the sample container cap from the sample container, and whereinthe sample container holder is configured to automatically rotate in theother one of the clockwise rotational direction and thecounter-clockwise rotational direction while the second capping deviceengages the sample container cap in order to install the samplecontainer cap onto the sample container. The supplemental containerholder is configured to automatically rotate in one of a clockwiserotational direction and a counter-clockwise rotational direction whilethe second capping device engages the supplemental container cap inorder to remove the supplemental container cap from the supplementalcontainer, and wherein the supplemental container holder is configuredto automatically rotate in the other one of the clockwise rotationaldirection and the counter-clockwise rotational direction while thesecond capping device engages the supplemental container cap in order toinstall the supplemental container cap onto the supplemental container.The sample capping device and the supplemental capping devices may beoffset from one another on the tool head such that, when the samplecapping device is in a position to grip and remove the sample containercap, the supplemental capping device is in a position to grip and removethe supplemental container cap without further rotational movement ofthe head tool. Without limitation, the supplemental container is one ofa reagent container and an aliquot container.

Other and further aspects and features of the disclosed embodiments willbecome apparent in view of the following detailed description to be readin conjunction with the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects of embodiments of the present disclosureare described in further detail with reference to the accompanyingdrawings, wherein like reference numerals refer to like elements and thedescription for like elements shall be applicable for all describedembodiments wherever relevant, and in which:

FIG. 1 is a right, front, perspective view of an exemplary automatedbiological sample processing system, according to one embodiment,including a sample processing cabinet, a slide printer, and an aliquotcontainer printer;

FIG. 2 is a right, front, perspective view of the sample processingcabinet of FIG. 1, wherein the exterior cabinet walls are not shown inorder to better show the system components located therein;

FIG. 3 is a left, front, perspective view of the sample processingcabinet of FIG. 1, wherein the exterior, and some interior, walls and/orpartitions are not shown in order to better show the system componentslocated therein;

FIGS. 4-14 are respective left, right and front perspective views of thesystem components of the sample processing cabinet of FIG. 1,illustrating the various movements and operations performed by thesystem components during a sample processing procedure;

FIG. 15 is an elevated side perspective view of the components carriedby a rotating tool head within the sample processing cabinet of FIG. 1,in which the covering of the tool is not shown;

FIG. 16 is a perspective view of the bottom of the sample processingcabinet of FIG. 1, in which a bottom cover plate is removed to revealthe system components; and

FIG. 17 is a perspective view of the back of the sample processingcabinet of FIG. 1, in which a bottom cover plate is removed to revealthe system components.

DETAILED DESCRIPTION

For purposes of illustration, the disclosed systems and methods of usedescribed herein and illustrated in the accompanying figures aredirected to the processing of a patient sample to produce a traditionalcytological specimen slide, it will be appreciated that alternativeembodiments may include the preparation of different types of biologicalspecimens that are presented on differing types of analytic elements(i.e., other than cytological and other than on a slide) arecontemplated within the scope of the disclosed embodiments and claims.Moreover, the disclosed systems and methods may be used for processingother types of liquid samples, including non-biological particulates andliquids. Thus, is should be understood that the disclosed andillustrated embodiments are presented for purposes of illustration andnot limitation.

As used herein, terms such “specimen”, “specimen sample”, “biologicalsample”, “cytological specimen”, “cell sample” and “biological specimen”may be used interchangeably and should be similarly understood andconstrued, unless the context of their use requires a more specificmeaning. Additionally, terms such as “aliquot” and “aliquot sample” maybe used interchangeably and should be similarly understood andconstrued. For example, and without limitation, the systems and methodsdisclosed herein may be used to process a biological sample contained ina liquid sample container to produce a specimen or a specimen sample, aswell as an aliquot or an aliquot sample. Moreover, the term “aliquot” isnot to be construed as limiting, as an “aliquot” is another way ofexpressing “liquid sample” or a “portion of a liquid sample.” In otherwords, to obtain an aliquot or an aliquot sample of a biological samplemeans to obtain and store a portion of the original sample in a separatecontainer for subsequent evaluation. Additionally, terms such as “samplecontainer”, “liquid sample container”, “patient container” “sample vial”and “patient vial”, “tube” “supplemental container” and otherpermutations may be used interchangeably and should be similarlyunderstood and construed, unless the context of their use requires amore specific meaning; for example, based on the stated contents of thecontainer.

As used herein, the terms “automatically” and “automated” mean that asystem, apparatus, process and/or function is performed without user(e.g., system operator) intervention, often but not necessarily underthe control of a programmed processor. In particular, the automatedsystems and methods disclosed herein advantageously reduce the number ofmanual steps required to prepare a biological sample, for example, theprepare a cytological specimen slide and/or to obtain an aliquot of apatient sample for additional testing and/or additional sampleprocessing, such as introducing a reagent into a sample prior to furtherprocessing.

FIG. 1 illustrates an exemplary automated biological sample processingsystem 10 that may be used for preparing a cytological specimen slideand/or an aliquot sample from a biological sample (e.g., obtained from apap smear) contained in a liquid sample container. As will be explainedin greater detail below, the system 10 may be used for additional typesof sample processing, such as (without limitation) for adding a reagentto a biological or other type of sample.

The system 10 generally includes a sample processing cabinet 11, a slideprinter 13 and an aliquot tube printer 19. In the illustratedembodiment, the main components of the system 10 are housed in (and/orattached to) a sample processing cabinet 11. As will be furtherdescribed below, a slide printer 13 and aliquot tube printer 15 areoperatively coupled with the sample processing cabinet via knownwireless or wired communication connections (not shown) under thecontrol of one or more processors located in the sample processingcabinet 11. For simplicity, the one or more processors are hereinafterreferred to collectively as a “system controller 60” (further describedbelow in conjunction with FIG. 17) that controls the automated movementsand other operations of the components of the system 10 housed withinthe sample processing cabinet 11, as well as the communications with therespective slide printer 13 and aliquot vial printer 19. For furtherease in describing the system 10, the components of the respectivesample processing cabinet 11, slide printer 13 and aliquot tube printer19 are referred to collectively as “the system” 10, without regard towhere the specific components may be housed. It should be appreciatedthat, in alternate embodiments, the various components of the system 10may be housed or otherwise provided separately.

By way of examples, and without limitation, the system 10 may beconfigured to process sample containers, such as the Thin Prep® samplevial, and aliquot containers such as the Aptima® vial, which are bothavailable from Hologic, Inc., Marlborough, Mass. (www.hologic.com).

The sample processing cabinet 11 is preferably an environmentallyenclosed housing (or “skin”) in order to reduce possible contaminationintroduced from the surrounding environment. In the illustratedembodiment, the sample processing cabinet 11 is provided with anopenable front door 15 to provide access to the system componentstherein. The door 15 is hinged such that it swings open and closed andis provided with a handle 29. In alternative embodiments, the door 15may be a sliding door, e.g., which slides laterally to open and close.In the illustrated embodiment, the front door 15 has a transparent orsemi-transparent panel so that the system components housed in thesample processing cabinet 11 are visible with the front door 15 in theclosed position, although this is not a requirement for practicing thedisclosed embodiments. With brief reference also to FIG. 16, astabilizing foot 79 that may be made of a material to minimizevibrational movement of the cabinet may be provided at each of the fourcorners of the bottom, wherein the cabinet would typically rest on thefour feet on a table top in a laboratory. The feet 79 are preferablysized and configured to allow for some clearance from the table surface,in addition to providing better stability.

The slide printer 13 may be any commercially available slide printer,such as the Signature Slide Printer available from Primera, Technology,Inc., located in Plymouth, Minn.(https://www.primera.com/signature-slide-printer). The slide printer 13is loaded with new slides, and outputs printed slides through an outputslot 17 that is be used for receiving a cytological specimen thereon aspart of the processing of a respective patient sample container. Inparticular, the printer 13 prints indicia (e.g., a bar code) onto aportion of the slide that is to the side of where the cytologicalspecimen is applied, wherein the printed indicia on the slide thatmatches or otherwise corresponds to indicia read on the sample containerbeing processed, as explained in further detail below.

The aliquot container printer 19 is preferably the same as taught inU.S. Pat. No. 9,724,948 (the '948 patent), the disclosure of which isincorporated herein by reference in its entirety. As explained by the'948 patent, the aliquot container printer 19 is provided with anopening 21 into which a new (unprinted) aliquot is inserted. The printer19 prints indicia (e.g., a bar code) on the aliquot container thatmatches or otherwise corresponds to the indicia read on the samplecontainer being processed, as explained in further detail below. Theprinted container is then ejected out of, or otherwise available forretrieval from, the opening 21.

FIGS. 2 and 3 depict the components of the system 10 that are housedwithin or otherwise attached to the sample processing cabinet 11,wherein the cabinet housing walls are removed for ease in illustration.The cabinet 11 comprises a chassis 14 which may include a plurality offloors, walls, and/or supports that provide a primary support structureto which the various system components are installed/mounted.

As best seen in FIG. 3, a cylindrical sample container holder 16 isdisposed in a lower central portion of the chassis 14. As will bedescribed in greater detail below, the sample container holder 16 isfixedly mounted on a rotating platform configured to rotate a samplecontainer 12 (shown in FIG. 4) held in the sample container holder 16about a center z-axis of the container 12 for mixing the sample forachieving a substantially uniform dispersion of the cellular or otherparticular material contained in the sample container 12 prior toinitiation of the processing thereof, and also to facilitate theuncapping and re-capping of the container 12 during the processing. Inthe illustrated embodiment, the sample container holder 16 is acylindrical receptacle configured to snuggly receive and hold the samplecontainer 12. The sample container holder 16 has an outer wall thatextends to a height less than the height of the sample container 12 suchthat a cap 43 on a sample container held in the sample container holder16 is completely exposed in order to facilitate the respective mixing,uncapping and capping thereof. In alternate embodiments, the samplecontainer holder 16 may be any suitable shape for receiving theparticular sample container being utilized with the system 10, such as arectangular box or other shape.

As also best seen in FIG. 3, an aliquot container holder 18 is disposedin a lower central portion of the chassis 14 directly in front of thesample container holder 16. As will be described in greater detailbelow, the aliquot container holder 18 is fixedly mounted on a rotatingplatform configured to rotate an aliquot container 20 (shown in FIG. 5)held in the aliquot container holder 18 about a center z-axis of thecontainer 20 to facilitate the uncapping and re-capping of the container20 during the sample processing. The aliquot container holder 18 isconfigured to snuggly receive and hold the aliquot container 20 and hasan outer wall that extends to a height less than the height of thealiquot container 20 such that a cap 45 on the aliquot container 20 heldin the aliquot container holder 18 is completely exposed in order tofacilitate the respective mixing, uncapping and capping thereof. In theillustrated embodiment, the aliquot container holder 18 is sized andconfigured to hold a more tubular shaped container than that held by thesample container holder 16. In alternate embodiments, the aliquotcontainer holder may be any suitable shape for receiving the particularaliquot container being utilized with the system 10, such as arectangular box or other shape. As is also described below, the system10 may be used to for additional sample processing steps, such as forintroducing a reagent into the sample container. As such, it should beunderstood that reference to the aliquot container holder 18 and thealiquot container 20 itself should be understood to be exemplary and notlimiting. For example, the term “supplemental container holder” and“supplemental container” may be used interchangeably with aliquotcontainer holder and aliquot container.

More particularly, the sample container holder 16 and aliquot containerholder 18 are each mounted on (or otherwise integrally formed with)respective underlying rotatable platforms (not shown) that are rotatablycoupled to or near a floor of the chassis 14. The respective rotatingplatforms, and thus the container holders 16 and 18, may be selectivelyrotated about a center z-axis of each holder 16 and 18 in a clockwiserotational-direction or a counter-clockwise rotational direction. Inparticular, and with additional reference to FIG. 16, a sampledispersion drive assembly is provided for performing relativelyhigh-speed mixing of the contents of a sample container 12 held in thesample container holder 16 in order to disperse the cellular and/orother particulate matter suspended within the liquid sample prior tofurther processing of the sample. The sample dispersion rotational driveassembly includes a sample dispersion motor (not seen) mounted proximatea floor of the chassis 14, the sample dispersion motor having a rotatingoutput shaft that extends through the chassis floor to rotate a drivewheel 81. The drive wheel 81 in turn rotates a larger diameter drivewheel 93 via a drive belt 88. A hi/lo speed clutch 82 is operativelycoupled with drive wheel 93 to selectively engage the drive wheel 93with the respective rotating platform associated with the samplecontainer holder 16 via a rotating drive shaft (not shown) extendingback up through the chassis floor, to thereby also rotate the samplecontainer holder 16 for performing relatively high-speed dispersion ofthe particles contained in a sample container 12 heled therein prior tofurther processing of the sample.

With continued additional reference to FIG. 15, the system 10 furtherincludes a capping drive assembly for providing simultaneous relativelylow-speed rotation of both the sample and aliquot container holders, 16and 18, for removing and reinstalling respective caps, 43 and 45, onsample and aliquot containers, 12 and 20, held in the respective sampleand aliquot container holders, 16 and 18, as is described below ingreater detail. The capping drive assembly includes a capper motor 39(seen in FIG. 3) mounted on or near the floor of the chassis 14 in alower side compartment 28 of the cabinet 11. The capper motor isreversible in order to provide rotational motion in each of a clockwisedirection and counter-clockwise direction. The capper motor 39 has arotating output shaft that extends through a floor of the chassis 14 torotate a drive gear 84, which in turn rotates a larger drive gear 91 viaa drive belt 85. The hi/lo speed clutch 82 is operatively coupled withthe drive gear 91 to thereby selectively engage the drive gear 91 withthe rotating platforms associated with the sample container holder 16and aliquot container holder 18 via a rotating shaft (not shown) thatextends from the drive gear 91 back up through the chassis floor.Notably, a further arrangement of one or more drive gears/wheels andbelts (not shown) are provided in a lower portion of the chassis,underlying the respective rotating platforms of the sample containerholder 16 and aliquot container holder 18 in order to simultaneouslydistribute the rotational motion of wheel 91 to each of the rotatingplatforms. In this manner, actuating of the capping motor simultaneouslyrotates the sample container holder 16 and the aliquot container holder18 at a relatively low-speed for removing or reinstalling the caps 43and 45, depending on the rotational direction of the output shaft of themotor 39.

Referring to FIG. 4, the system 10 includes an automated tool head 30that is rotatably mounted on a load bearing shaft assembly 34, such thatthe tool head 30 is configured to pivot or rotate back and forth about arotational axis, indicated by dashed line 33 in FIG. 7. Preferably, thetool head 30 has a range of rotation through an arc of at least 270degrees about the rotational axis, although no specific minimum amountof rotational travel s is required beyond that necessary to perform thefunctions of the particular system embodiment. In the illustratedembodiment, the tool head rotates at least 270 degrees about itsrotational the axis 33. The load bearing shaft assembly 34 preferablyincludes spin bearings (not shown) to minimize friction between the toolhead 30 and a mounting shaft (not shown) on which the tool head 30. Atool head rotational actuating motor 36 is attached to the load bearingshaft assembly 34, wherein an output shaft (not seen) of the motor 36 isoperatively coupled to the shaft in or to rotate the tool head 30 via adrive belt 74. The rotational actuating motor 36 is reversible toselectively provide rotational motion of the tool head 30 in both aclockwise rotational direction and a counter-clockwise rotationaldirection.

With continued reference to FIG. 4, the motor 36 is housed in ablock-type support housing (also referred to as item 36 in the figures),which is threadably mounted on a vertical lead screw 55 (best seen inFIG. 15) disposed in a rear portion of the chassis 14. The lead screw 55is actuated by a tool head linear actuating motor 32 mounted to a rearwall (near the top) of the chassis 14. The tool head linear actuatingmotor 32 is reversible to selectively provide rotational motion of thelead screw 55 in both a clockwise rotational direction and acounter-clockwise rotational direction. In particular, rotation of thelead screw 55 in one of the clockwise rotational direction and acounter-clockwise rotational directions causes the motor block 36, andthus the respective load bearing shaft assembly 34 tool head 30, totravel linearly upward relative to the chassis 14 along a vertical (or“z”) translational axis indicated by dashed line 51 in FIG. 4, androtation of the lead screw 55 in the other one of the clockwiserotational direction and a counter-clockwise rotational directionscauses the motor block 36, and thus the respective load bearing shaftassembly 34 tool head 30, to travel linearly downward relative to thechassis 14 along the vertical axis 51. With this mechanical arrangement,and as further described below, the automated tool head 30 is configuredto selectively controllably rotate in each of a clockwise rotationaldirection and a counter-clockwise rotational direction about therotational axis 33, and to independently selectively translate up ordown along the vertical axis 51, respectively, including simultaneousrotational and translational motion. Operation of the rotationalactuating motor 36 controls the rotational position of the tool head 30about the rotational axis 33, and operation of the linear actuatingmotor 32 controls the vertical position of the tool head 30 along thevertical axis 51 within the interior of the cabinet 11.

A number of sample processing devices (or “tools”) are disposedcircumferentially about the tool head 30, and are arranged so that therespective function accomplished by each of the devices may beaccomplished by one or both of one or both of rotation of the tool headabout its rotational axis 33 and translation of the tool head 30 alongits vertical translation axis 51, without requiring movement of the toolhead 30 in an x direction (i.e., sideways relative to the cabinet 11),or a y direction (i.e., back to front relative to the cabinet 11). Inthe illustrated embodiment, these devices include an indicia reader 31configured to read an indicia such as a bar code on the sample container12; a first capping device 42 including pneumatically controlledgrippers configured for releasably griping a cap 43 of a samplecontainer 12 being processed; a second capping device 44 includingpneumatically controlled grippers configured for releasably griping acap 45 of a supplemental container 20 (e.g., an aliquot tube or a vesselcontaining a reagent); a pipettor 37 (best seen in FIG. 15) having apipette tip engaging member 38 extending outwardly from the tool head 30and configured for releasably engaging pipette tips; a specimencollection and transfer device (hereinafter “specimen transfer device”)40 having a working end extending outwardly from the tool head 30 andconfigured for obtaining a specimen sample from the sample container;and a slide loading bed or “platform” 46 configured to receive a slide50 to be delivered by the tool head 30 to a slide holder 57 of a slidepositioner assembly 56 (as described below in greater detail).

Each of devices 31, 42, 44, 37/38, 40 and 46 is located on the tool head30 a different circumferential and/or angular position and orientationabout the rotational axis 33, so as to that each of these devices rotatewith the tool head 30 as the tool head is rotated about its rotationalaxis 33 under control of the rotational actuating motor 34, and aremoved vertically up or down within the interior of the cabinet 11 alongvertical axis 51 of the tool head under control of the translationalactuating motor 32. Thus, the rotational and/or vertical translationalactuation of the tool head 30 positions each of these devices at arelative rotational and vertical position within the interior of thecabinet 11 in order to perform their respective functions, as furtherdescribed herein. It should be appreciated that each of the particulardevices or tools provided on the tool head 30 in the illustratedembodiment is not essential, nor limiting. For example, in alternativeembodiments, more or less devices/tools may be carried on the tool head30. For example, only a single capping device (e.g., 42 or 44) may beemployed and/or the reader 31 may be provided in a location separatefrom the tool head 30, including not being within the cabinet 11. By wayof further example, the slide loading platform 46 may be omitted in someembodiments, wherein the system operator loads the slides directly intoa slide holder such as or similar to slide holder 57. These and othervariations and permutations of the provisional of devices/tools on thetool head 30 are also contemplated within the scope of the presentdisclosure.

As seen in FIGS. 3 and 4, a pump 47 having a pump head 49 suppliespressurized air that is stored in a high-pressure tank 71 that suppliespressurized air for operating various pneumatic devices location in thecabinet 11 via manifold of solenoid valves 68 and connectors 67. Aslightly elevated pressure tank 72 and a slightly negative pressure tank73, respectively, are also provided for operation of the specimentransfer device 40 (described below in greater detail). For clarity,communication pathways of the pressurized air, such as solid and/orflexible tubing lines interconnecting the pump 47 to the tank 71, andthe tank 71 to the various pneumatic devices are not shown in order tomore clearly view the system components located in the cabinet 11without being obscured by the tubing. However, a flexible conduit 23through which various pneumatic tubing and electrical conducts areconnected to the tool head 30 and the various devices thereon, such as(without limitation) the cappers 42, 44, pipettor 37 and the specimentransfer device is shown in FIG. 2 (only). Bundling the various tubingand wires through the single conduit 23 reduces the chance of snaggingor displacing a tube or wire from a connector by operation of the toolarm 30. Notably, the lengths of the tubing and electrical connectionsthat pass through the conduit 23 are sufficiently long to allow theconduit 23 can to move with the tool head 30 as the tool head 30translates linearly along its vertical axis 51 and rotates about itsrotational axis 33.

Referring back to FIGS. 2 and 3, the reader 31 is configured to readidentifying indicia such as (without limitation) patient identificationand/or medical record identifiers, a date on, or medical establishmentat, which the sample was obtained, etc., on any of the sample container12, aliquot container 20, slide 50 and/or filter 54. The reader 31 maybe an optical reader or scanner, such as for reading barcodes, QR codes,machine readable alphanumeric text and/or an optical camera thatacquires an image of a label that may then be read and/or recognizedusing optical character recognition (OCR) software, or an electronicreader configured to read an NFC chip, RFID or other electronic tag, orother reader configured to read a readable indicia. Examples of suchalternate indicia storage techniques for slides are provided in U.S.Pat. No. 7,083,106 and U.S. Pat. Publ. No. 20070148041, the disclosuresof which are incorporated herein by reference in their entirety. In theillustrated embodiment, the reader 31 is configured among othercapabilities to read indicia in form of a bar code. Indicia on thesample container 12 is read by the reader 31 and transmitted via thesystem controller 60 (described below in further detail) to each of theslide printer 13 and the aliquot container printer 19 for printing amatching or otherwise corresponding indicia on a respective slide 50and/or aliquot container 20 to be used in a sample processing procedure.

With reference (primarily) to FIGS. 2-5, a pipette tip dispenser gantryor “transporter” 22 is coupled to the chassis 14 forward of the aliquotcontainer holder 18. The pipette tip dispenser transporter 22 includes apipette tip dispenser holder 24 configured for securely seating apipette tip dispenser 26 thereon. The pipette tip dispenser isconfigured for holding a plurality of pipette tips 48, e.g., eightpipette tips in the illustrated embodiment, wherein the dispenser may besupplied as a pipette tip cartridge. The pipette tip dispenser 26 may beremovably mounted to the holder 24 in any of a number of ways. In theillustrated embodiment, the pipette tip dispenser 26 is magneticallycoupled to the pipette tip dispenser holder 24 in a manner that ensuresprecise and predictable positioning of the dispenser 26 relative on theholder 24, and which also allows for the system controller 60 (furtherdescribed below) to confirm through a sensor circuit that the dispenser26 is properly attached and positioned relative to the holder 24. Thisis important to ensure that the pipette tip engaging member 38 carriedby the tool head 30 can exactly align with, to thereby engage a pipettetip 48 held in a respective slot of the dispenser during a sampleprocessing procedure.

With brief reference also to FIG. 16, lateral translation of the pipettetip dispenser transporter 22 is performed by a motorized drive belt 87that spins back and forth on drive wheels 80 a and 80 b underlying abottom surface of the chassis 14. The drive wheels in turn rotaterespective shafts (not shown) that extend back through the chassis floorand are mechanically coupled to the transporter 22 for translating sameto laterally move the pipette tip holder 24 and the pipette tipdispenser 26 mounted thereon between a storage position, in which thepipette tip dispenser is located within an isolation chamber 28, asshown in FIG. 4, and a loading position as shown, in which a slot of thepipette tip holder 26 containing an available pipette tip 48 is alignedwith the pipette tip engaging member 38 on the tool head 30, as shown inFIG. 7. In particular, the loading position will vary depending uponwhich slot(s) of the dispenser 26 are occupied by pipette tips. In thestorage position, the respective pipette tip holder 24, and the pipettetip dispenser 26 mounted thereon, are positioned within an isolationchamber 28 located within the sample processing cabinet 11 in order toreduce the chances of contamination of unused tips from the sampleprocessing activities taking place in the main interior region of thecabinet 11.

As can be seen by comparing FIG. 4 and FIG. 5, a panel 52 (FIG. 4) isattached to a side of the pipette tip dispenser 26 and is sized andshaped to close an opening through which the holder 24 and dispenser 26enter the isolation chamber 28. As seen in FIG. 3, a pipette tip sensor35 located in the isolation chamber 28 tracks the pipette tips 48 heldin the dispenser 26 to inform the system controller 60 on same forprecisely moving the pipette tip dispenser transport 22 to a location inwhich a tip 48 held in the dispenser 26 is aligned with the pipette tipengaging member 38 on the tool head 30, and also to ensure that thereare adequate pipette tips available in the dispenser 26 to perform theparticular sample processing procedure. If the dispenser 26 is empty orotherwise holds an insufficient amount of pipette tips 48 to perform aparticular sample processing procedure, then system 10 will pause andnot perform any further sample procedures until new pipette tips 48 havebeen loaded into the dispenser 26.

A used pipette tip waste bin 25 is mounted on a separate platform/holder27 attached to the pipette tip transporter 22, wherein the pipette tipdispenser transporter is configured to selectively translate the pipettetip waste bin 25 to a location at which the tool head 30 positions thepipette tip engaging member 38 to disengage an engaged pipette tip 48into the waste bin 25. As with the pipette tip dispenser 26 and holder24, the waste bin 25 is preferably magnetically coupled to holder 27 forboth providing stability and to allow the system 10 to confirm via asensing circuit that the waste bin is properly attached. In particular,the pipette tip waste bin holder 27 is mounted on the pipette tiptransporter 22 relative to the pipette tip dispenser holder 24 suchthat, when the pipette tip dispenser 26 is translated into the isolationchamber 28, the pipette tip waste bin 25 is simultaneously translated tothe location at which the tool head 30 positions the pipette tipengaging member 38 to disengage an engaged/used pipette tip 48 into thewaste bin 25.

With reference also to FIG. 15, the pipettor 37 is disposed on the toolhead such that the pipette tip engagement member 38 is at a slight anglerelative to the pipette tip dispenser 26. Similarly, are slightly angledso that the engaging member can mate to thereby engage a pipette tip 48held in one of the slots by one or both of rotational and translationalmotion of the tool head 30. The pipettor 37 may be, for example andwithout limitation, a Cavro® Air Displacement Pipettor (ADP) sold byTecan Group Ltd. (www.tecan.com/components), having including a springbiased engaging tip 53 (shown in FIG. 15) that releasably engages therespective pipette tips by a compression fit of the engaging tip 53 asit is inserted into the bore of a respective pipette tip 48. Once apipette tip 48 is engaged (or installed) on the pipette tip engagingmember 38, the pipettor 37 is configured to selectively draw liquid froma sample container 12 into the pipette tip 48, and to dispense the drawnliquid contained in the pipette tip 48 into an aliquot container 20,respectively.

In this manner, during a sample processing procedure, the pipettor 37engages a pipette tip 48 from the pipette tip dispenser 26. The pipettoris then repositioned by the tool head 30 to position the engaged tipinto an open container (e.g., an open sample container 12). In a knownfashion, the pipette tips 48 are made of a conductive material (such asa conductive polymer) in order to use an impedance sensing circuit ofthe pipettor 37 to confirm that the pipette tip 48 is submerged in theliquid for drawing a sample, e.g., an aliquot from the sample container,by supplying a vacuum within the bore of the pipette tip 48 to therebydraw a volume of the sample into the pipette tip 48. The pipettor 37dispenses the sample drawn into the pipette tip 48, e.g., into an openaliquot container 20, by releasing the vacuum allowing the sample todispense out of the pipette tip 48. The pipettor 37 is configured andoperates such that only the pipette tip 48 comes into contact with thesample material so that the pipette tip engaging member 38 of thepipettor 37 is not contaminated by the sample material. The pipette tipengaging member 38 is configured to disengage the pipette tip 48 intothe waste container 25 after use by movable displacement sleeve thatpushes the tip 48 off the tip 53 of the pipette tip engaging member 38.

The specimen transfer device 40 is carried by the tool head 30 and isconfigured to collect a specimen sample from the sample in the samplecontainer 12 and to transfer the collected specimen sample to a slide50. In the described embodiment, the specimen transfer device 40includes a cylindrical working end portion that extends away from thetool head 30 and is configured to form a pressure-tight seal around itscircumference with a filter 54 that is seated thereon prior toinitiating a sample processing procedure, as shown in FIG. 4. The filter54 includes a hollow cylindrical body having an open proximal end and amembrane spanning across its distal end having pores of a selected sizeto capture desired cells for the specimen sample and to pass smallercells and non-cellular particles and liquids therethrough. Embodimentsof the filter 54, as well as of specimen sample collection and transferdevices and techniques suitable for use with the illustrated system 10are disclosed and further described in U.S. Pat. No. 8,119,399, U.S.Pat. Publ. No. 20050100483 and U.S. Pat. Publ. 20080145887, thedisclosures of which are incorporated herein by reference in theirentirety. When installed on the working end of the specimen transferdevice 40, the filter 54 extends away from the tool head 30 by asufficient distance to allow the filter to be inserted into the samplecontainer 12 to collect a specimen sample on the membrane of the filter54 without the sample liquid coming into contact with any part of thespecimen transfer device 40, such that only the filter contacts thesample liquid. This ensures that the specimen transfer device 40 is notcontaminated by the sample material when it collects a specimen samplefrom the sample container 12. Once the specimen transfer device 40 hascollected a specimen onto the sample collector 54, it is thenmanipulated to transfer the specimen from the filter 54 to the slide 50,as described in more detail below.

In particular, the specimen transfer device 40 and the system 10 areconfigured to insert the membrane of the filter into the sample in thesample container via one or both of translational and rotational motionof the tool head 30, and to force the sample back and forth through themembrane to collect the specimen sample onto the membrane in a “sipping”manner, which deposits a thin layer of cells in the liquid sample ontothe outside surface of the membrane. The specimen transfer device 40 maybe configured to cycle a vacuum (and pressure) within the working end ofthe specimen transfer device in order to force the sample back and forththrough the membrane. In addition, or alternatively, the specimentransfer device 40 and system 10 may be configured to move the membraneup and down within the sample in order to force the sample back andforth through the membrane in order to collect the specimen sample onthe membrane. Methods and apparatus for determining whether a sufficientamount, but not too many, cells have been collected by on the filtermembrane using this same “sipping process” are disclosed and describedin the above-incorporated U.S. Pat. No. 8,119,399. Further details ofthe specimen collection process in general, and of design and operationof the specimen transfer device 40 (and filter 54) is found in to U.S.Pat. No. 8,137,642, the disclosure of which is incorporated herein byreference in its entirety, as well as several other of theabove-incorporated patents. With brief reference to FIG. 17, wasteliquid from the specimen collection process is removed out of ports 95located in the back of the cabinet 11.

The sample container capping device 42 comprises movable pneumaticprongs or “grippers” configured to grip and hold a cap 43 of a samplecontainer 12. As can be seen in FIG. 15, the grippers are actuated by apneumatic force supplied on an actuation member 77 to alternativelyprovide a tweezer-like radially inward gripping motion, or a radiallyoutward release motion. The two or more grippers are preferably disposedsubstantially evenly about the circumference of the sample container cap43 and can be placed into a “capping” or “uncapping” position by one ormore of translational and rotational motion of the tool head 30. In thecase of removing the cap 43, the capper 42 grips the cap 43 while thecontainer holder 16 is rotating in one of a clockwise direction orcounterclockwise direction, and the tool head 30 rises slightly andsteadily upward to allow the cap 43 to travel upward as it rotates onthe threads (not shown) of the container 12. In the case of installing acap 43 that is held by the grippers back onto the container 12, the toolhead 30 positions the capper 42 over the open container and travelsslightly and steadily downward as the holder 16 rotates in the other ofthe clockwise direction and counter-clockwise direction while the toolhead 30 lowers slightly and steadily to allow the cap 43 to traveldownward onto the container 12, as the container is rotated by theholder 16 relative to the cap 43. The grippers used for the samplecontainer capping device 42, and also for the below described aliquotcontainer capping device 44 include Parallel Style Air Gripper/2 Finger,3 Finger and 4 Finger series grippers available from SMC Pneumatics.com.

The aliquot container capping device 44 operates substantially the sameway as the sample container capper, including using two or more prongsor grippers to releasably grip the cap 45 of an aliquot container 20while the aliquot container holder is rotated in a clockwise orcounterclockwise direction to respectively remove or install the cap 45from or onto the container 20. Again, the tool head 30 moves steadilydownward or upward to accommodate the motion of the cap relative to thecontainer 20 during the process. Notably, because less torqueing forceis needed for uncapping and capping the aliquot container 20, as seen inFIG. 15, direct air pressure supplied through hose attachments 75 isused to power the aliquot container grippers.

The sample container capping device 42 and the aliquot container cappingdevice 44 are preferably positioned and oriented on the tool head 30 sothat both capping devices 42 and 44 are in proper position to remove therespective caps 43 and 45 without requiring repositioning of the toolhead 30.

It should be appreciated that, in alternate embodiments, the respectivecappers 42 and 44 may be rotatable, in which case the capping processwould include having capper 42 grip cap 43 and rotate while the sampleholder remains stationary, and capper 44 grip caps 45 and rotate whilethe aliquot holder 18 remains stationary, such as taught in theabove-incorporated U.S. Pat. No. 9,335,336 and U.S. Pat. Publ. no.2017/0052205.

The slide loading platform 46 is preferably positioned on the tool head30 at a location convenient for a system operator to load a slide 50thereon prior to a sample processing procedure, and is configured toreceive and hold the slide 50 when it is loaded thereon. Although theloading platform 46 in this described embodiment is configured toreceive and hold a microscope slide as the slide 50, it is to beunderstood that the loading platform 46 may be configured to receive andhold other types of analytic elements other than slides, depending onthe type of sample specimen to be output by the system 10.

As mentioned above, the slide positioner 56 includes a slide holder 57having pneumatic grippers 59 configured to grip and remove a slide 50from the loading platform 46 (the transfer is seen in FIG. 5), and tothereafter position the slide for receiving the specimen sample obtainedby the specimen transfer device 40. The slide positioner is also movablein at least two degrees of freedom supplied by a slide positioner motor63, and various hinged arms, and is supported by a counterweight 64.After the membrane of the filter 54 is pressed against the slide 50 totransfer the specimen sample (FIG. 12), the slide positioner moves androtates the slide 50 90 degrees proximate an open container of fixative58 seated in a fixative container holder 61 includes a slide positioner56 which is configured to grip and move the slide 50. Towards this end,the slide positioner 56 includes a pneumatically controlled gripper 59configured to grip and thereby remove the slide 50 from the loadingplatform 46, as shown in FIG. 5. The slide positioner 56 then moves theslide to a transfer position in which the specimen transfer device 40can transfer a specimen sample from the filter 54 to the slide 50 asshown in FIG. 11, and then to a fixative position in which the analyticpositioner 50 can place the slide 50 into a fixative container 58containing a fixative for affixing the specimen sample to the slide 50.The system 10 includes a fixative container holder 61.

With reference to FIG. 17, the system 10 also includes one or moreprocessors that may be collectively referred to as a controller 60located in a back panel of the cabinet. The controller 60 is operativelycoupled to, and configured to communicate with, and to control theautomatic operation of, the various components of the system 10,including the tool head 30, tool head actuator 32, pipettor 37, specimentransfer device 40, first capping device 42, second capping device 44,slide positioner 56, and reader 31. The controller 60 includes acomputer processor, input/output interfaces and other supportingelectronics for communicating with and controlling the operation of thecomponents of the system. The controller 60 has a user input device forallowing a system operator to input commands, data, etc. into thecontroller 60. The user input device may be a touchscreen/display 62, asdescribed below. The controller 60 also has system software forprogramming the controller 60 to communicate with and control the system10 to perform the process of preparing a sample specimen and/or analiquot sample from a biological or other sample contained in a samplecontainer 12, as described herein. In the illustrated embodiment. Thetouchscreen/display 62 is attached to the chassis and preferablyintegrated into the cabinet housing so as to be disposed to allow asystem operator to input instructions (for example, if prompted by thesystem 10), and review status of the items performed during a sampleprocessing procedure. The touchscreen/display 62 is configured fordisplaying graphics generated by the controller 60, includinginformation regarding the operation of the system 10, such as status ofthe operation, data, etc. The touchscreen/display 62 may be any suitabledisplay such as a liquid crystal display (LCD), LED display, AMOLED,etc.

An exemplary sample processing procedure will now be described withreference to FIGS. 1-14 in order to further illustrate and describe thevarious elements and components of the system 10. In particular, theexemplary sample processing includes initially obtaining an aliquot ofthe sample, and thereafter processing the sample to create a biologicalspecimen slide. This process is described for purposes of illustration,and not limitation, and it should be understood that other types ofsample processing may be performed using the disclosed and describedsystem and variations thereof, while remaining within the scope of thepresent disclosure. By way of example and without limitation, each ofthe method of using an automated system to process a sample contained ina sample container set forth in the appended claims hereto should beconsidered as additional exemplary sample processing procedures that maybe performed using the illustrated system 10.

To initiate processing of a given patient sample container 12, a systemoperator enters an instruction for same, e.g., by contacting a “startbutton” or similar symbol on the user interface 62. The systemcontroller 60 causes the tool head 30 to assume an “initiation” position(if the tool head 30 is not otherwise not already in this position), inwhich the tool head 30 is positioned and rotated within the cabinet 11to position the reader 31 in a convenient location for the systemoperator to present the sample vial 12, such as seen in FIG. 4.

After receiving a visual confirmation from the system controller 60 onthe user interface display 62, the system operator presents the samplecontainer 12 to the reader 31, so a patient and/or other indicia on thesample container 12 is within the field of view of the reader 31. Thereader 31 reads the indicia on the sample container 12 and communicatessame (via the controller 60) to the respective slide printer 13 andaliquot container printer 19. The slide printer automatically prints andoutputs a new (i.e., unused) slide 50, wherein indicia matching orotherwise corresponding to the indicia on the sample container 12 isprinted on the slide 50. The system operator also inserts a new (i.e.,unused) aliquot container 20 into the aliquot container printer, whichprints indicia on the aliquot container 20 that also matches orotherwise corresponds to the indicia on the sample container 12.

The pipette tip dispenser transporter 22 is moved to the loadingposition (FIG. 2) to expose the pipette tip dispenser 26 in caseadditional tips 48 must be added. Loading the system 10 with the samplecontainer 12, the aliquot container 20, the slide 50 and the pipette tipdispenser 26 may be automated using automation such as robots, or it maybe performed manually by a system operator—the later being assumed inthis example for simplification. In particular, the system operator thenloads the (capped) sample container 12 into the sample container holder16 and loads the (capped) aliquot container 20 into the aliquotcontainer holder 18, in each case after having the reader 31 read andconfirm that the respective sample and aliquot container indicia match.The system operator loads the slide 50 onto the slide loading platform46 in a face down orientation, i.e., with the side of the slide havingthe printed indicia and the “cell spot” area to receive the specimensample facing downward into the platform 46, The system operator andloads a new filter 54 onto the working end of the specimen transferdevice 40, and confirms that there are an adequate (at least one) numberof unused pipette tips 48 in the pipette tip dispenser 26 and that thepipette tip waste bin 25 is empty. Once all of the consumables areloaded, the system operator closes the door 15 of the cabinet 11 andindicates via the user interface that the sample processing proceduremay be commenced, assuming all of the system verifications are complete.

Notably, the system 10 will not initiate the sample processing procedureunless the sensor 35 indicates that a sufficient number of pipette tips48 are in the dispenser 26, even if this means just one, and also thatthe pipette tip dispenser 26 and waste bin 25 are properly seated andmagnetically coupled to their respective mounting platforms 24 and 27 onthe pipette tip dispenser transporter 22. The specimen transfer device40 performs a “dry” test to verify the integrity of the filter 54, inparticular, to confirm distal end membrane has not been punctured(indicating the filter 54 has been previously used) or otherwiseoccluded or torn. Notably, once it is confirmed that there are adequatepipette tips 48, the pipette tip dispenser transporter is moved by thesystem so that the pipette tip dispenser is located in the isolationchamber 28 From that point until the sample processing procedure iscompleted, no further system operator involvement is normally required.

As shown in FIGS. 4-6, at the beginning of the sample processingprocedure, the pipette tip dispenser transporter 22 moves the pipettetip dispenser into the storage position in the isolation chamber 28(FIG. 3), and the tool head 30 rotates slightly upwards and alsolinearly translates upward so that the slide 50 may be griped by thegrippers 59 of the slide holder 57. The tool head 30 then linearlytranslates downward and rotates so that the indicia on the side 50 maybe read by the reader 31 to confirm the indicia matches that of therespective sample container 12 and aliquot container 20. Assuming thematch is verified, the system 10 continues with the then performs anautomated process to prepare a specimen sample and an aliquot samplewith each of the components of the system 10 operated and controlled bythe controller 60.

As shown in FIG. 6, the tool head 30 is rotated and moved verticallydownward by the tool head actuator 34 to position the sample containercapping device 42 over the cap 43 on the sample container 42 and thealiquot container capping device 44 over the second cap 45 on thealiquot container 20. The respective capping devices 42 and 44 removeand grip the caps 43 and 45 in cooperation with rotation of therespective container holders 156 and 18.

As shown in FIG. 7, the pipette tip dispenser transporter 22 moves tothe loading position to position a pipette tip 48 contained in thepipette tip dispenser 26 to be installed on the pipette tip engagingmember 38 of the pipettor 37. Also shown in FIG. 7, the tool head 30rotates to position the pipette tip engaging member 38 to install thepipette tip 48 by respective rotation and translation of the tool head30 to push the pipette tip engaging member into the pipette tip 48.

As shown in FIG. 8, the pipette tip dispenser transporter 22 moves backto the storage position. The tool head 30 rotates and translatesvertically to place the pipette tip 48 on the pipettor 37 into thesample in the sample container 12. The pipettor 37 draws a vacuum withinthe pipette tip 48 to draw a volume of the sample (the aliquot sample)into the pipette tip 48.

As shown in FIG. 9, the tool head 30 rotates and translates verticallyto position the pipette tip 48 in the aliquot container 20. The pipettor37 releases the vacuum to dispense the aliquot sample out of the pipettetip 48 and into the aliquot container 20. After the aliquot sample hasbeen dispensed into the aliquot container 20, the tool head 30 isrotated and translated to position the aliquot container capping device44 in position to reinstall the cap 45 back onto the aliquot container20 (same position as shown in FIG. 6).

As shown in FIG. 10, the tool head 30 is rotated and translated toposition the pipette tip 48 over or within the waste container 25. Thepipette tip engaging member 38 then disengages (ejects) the used pipettetip 48 into the waste container 25.

As shown in FIG. 11, the tool head 30 is rotated and translated toposition the filter 54 installed on the specimen transfer device 40 inposition to collect a specimen sample from the sample container 20 ontothe filter membrane according to the process described above, i.e.,forcing the sample back and forth through the membrane either by acycling vacuum and/or by moving the filter up and down, such as bymoving the tool head 30 via the tool head actuator 34. This processallows a thin layer or single layer of cells, to be collected on themembrane.

As shown in FIG. 12, the tool head 30 is rotated and translated toposition the filter membrane in position to transfer the specimen sampleto the slide 50 held by the grippers 59 of the slide holding device 57.The specimen transfer device 40 and/or the slide positioner 56 are thenmanipulated to contact the membrane having the specimen sample thereononto the slide 50. The tool head 30 may be moved via the tool headactuator 34 to manipulate the specimen transfer device 40. In order toprovide for transfer of the specimen sample (e.g., a thin layer ofcells) to the slide 50 without disturbing the spatial distributionthereof, it is desirable that the membrane of the filter 54 firstcontact the slide 50 generally at a single location, forming apredetermined small pre-contact angle between the membrane and adeposition surface of the slide 50, and then gently and gradually enterinto complete contact with the slide 50. This may be accomplished bymanipulating the specimen transfer device 40 and the slide positioner 56in coordination.

As shown in FIG. 13, the tool head 30 is moved downward and may also berotated to provide room for the slide positioner 56 to place the slide50 having the specimen sample thereon into a fixative container 58containing fixative for affixing the specimen sample onto the slide 50.After transferring the specimen sample to the slide 50, the tool head 30translates and/or rotates to drive the filter membrane into a pin 41(FIG. 4) in order to destroy the filter membrane to prevent reuse. Asalso shown in FIG. 13, the slide positioner 56 is actuated to place theslide 50 having the specimen sample thereon into the fixative container58. Once the sample processing procedure is completed, a system operatormay remove the specimen slide 50 from the fixative solution in container58, or alternatively may remove the fixative container, including thespecimen slide 50, and replace the fixative container 58 (or place a newone) in the holder 61 prior to commencing a new sample processingprocedure.

The tool head 30 is rotated and moved downward to position the samplecontainer capping device 42 in position to reinstall the cap 43 backonto the sample container 12 (same position as shown in FIG. 4).

This completes the automated process for preparing the specimen sampleand aliquot sample. The slide 56 having the specimen sample affixedthereon by the fixative can then be removed from the fixative container58 and utilized for testing. The sample container 12 and the aliquotcontainer 20 may also be removed from the system 10 and storedappropriately. The waste container 25 is removed from the system 10 anddumped into a waste bin to dispose of the used pipette tip 48. The wastecontainer 25 may then be placed back onto the waste container platform27.

The process as described may be repeated for additional samplecontainers having respective sample contained therein, as desired.

Although particular embodiments have been shown and described, it is tobe understood that the above description is not intended to limit thescope of these embodiments. While variations of the many aspects of theherein disclosed embodiments have been illustrated disclosed anddescribed, it should be appreciated that the foregoing disclosure isprovided for purposes of explanation and illustration only, and thatvarious changes and modifications may be made to the disclosedembodiments without departing from the scope of the following claims.For example, not all of the components depicted and described in theembodiments are necessary, and the alternative embodiments may includeany suitable combinations of the described components, and the generalshapes and relative sizes of the components may be modified.

What is claimed is:
 1. An automated system for processing a samplecontained in a liquid sample container, the system comprising: a samplecontainer holder configured for holding a sample container; an automatedtool head configured to rotate about a first axis, and to translatealong a second axis different than the first axis; a first cappingdevice disposed at a first circumferential position on the tool headsuch that the first capping device rotates with the tool head as thetool head is rotated about the first axis, the first capping deviceconfigured to controllably grip and release a cap of a sample containerheld in the sample container holder, wherein the tool head is configuredto automatically position the first capping device proximate the samplecontainer cap through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis, andwherein the first capping device operatively cooperates with the samplecontainer holder to remove or install the sample container cap; ananalytic element positioner having an analytic element holder configuredto releasably grip an analytic element; and a specimen transfer devicecarried by the tool head at a second circumferential position on thetool head angularly spaced apart about the first axis from the firstcircumferential position such that the specimen transfer device rotateswith the tool head as the tool head is rotated about the first axis,wherein the tool head is configured to automatically position a workingend of the specimen transfer device to obtain a specimen from a samplecontainer held in the sample container holder, and to transfer theobtained specimen to an analytic element held by the analytic elementholder, respectively, through one or both of rotation of the tool headabout the first axis and translation of the tool head along the secondaxis.
 2. The system of claim 1, wherein the sample container holder isconfigured to automatically rotate in one of a clockwise rotationaldirection and a counter-clockwise rotational direction while the firstcapping device engages the sample container cap in order to remove thesample container cap from the sample container, and wherein the samplecontainer holder is configured to automatically rotate in the other oneof the clockwise rotational direction and the counter-clockwiserotational direction while the first capping device engages the samplecontainer cap in order to install the sample container cap onto thesample container.
 3. The system of claim 1, further comprising a pipettetip dispenser; and a pipettor carried by the tool head, the pipettorhaving a pipette tip engaging member configured to releasably engagepipette tips, wherein the tool head is configured to automaticallyposition the pipette tip engaging member proximate the pipette tipdispenser to allow the pipette tip engaging member to engage a pipettetip held by the pipette tip dispenser through one or both of rotation ofthe tool head about the first axis and translation of the tool headalong the second axis.
 4. The system of claim 3, further comprising apipette tip dispenser transporter, wherein the pipette tip dispenser ismounted on the pipette tip dispenser transporter, the pipette tipdispenser transporter configured to translate the pipette tip dispenserrelative to the tool head so that the pipette tip dispenser may beselectively translated to a location at which the tool head positionsthe pipette tip engaging member to engage a pipette tip from the pipettetip dispenser.
 5. The system of claim 4, further comprising a pipettetip dispenser isolation chamber, wherein the pipette tip dispensertransporter is configured to selectively translate the pipette tipdispenser between the location at which the tool head positions thepipette tip engaging member to engage a pipette tip from the pipette tipdispenser and a second location within the isolation chamber.
 6. Thesystem of claim 4, further comprising a pipette tip waste bin mounted onthe pipette tip transporter, wherein the pipette tip dispensertransporter is configured to selectively translate the pipette tip wastebin to a location at which the tool head positions the pipette tipengaging member to disengage a pipette tip into the pipette tip wastebin.
 7. The system of claim 3, further comprising a supplementalcontainer holder configured for holding a supplemental container,wherein the tool head is configured to automatically position thepipette tip engaging member into a position in which a pipette tipengaged on the pipette tip engaging member is inserted into a samplecontainer held in the sample container holder, and into a position inwhich the engaged pipette tip is inserted into a supplemental containerheld in the supplemental container holder, respectively, through one orboth of rotation of the tool head about the first axis and translationof the tool head along the second axis.
 8. The system of claim 7,further comprising a second capping device disposed on the tool head andconfigured to controllably grip and release a cap of a supplementalcontainer held in the supplemental container holder, wherein the toolhead is configured to automatically position the second capping deviceproximate the supplemental container cap through one or both of rotationof the tool head about the first axis and translation of the tool headalong the second axis, and wherein the second capping device operativelycooperates with the supplemental container holder to remove or installthe supplemental container cap.
 9. The system of claim 8, wherein thesupplemental container holder is configured to automatically rotate inone of a clockwise rotational direction and a counter-clockwiserotational direction while the second capping device engages thesupplemental container cap in order to remove the supplemental containercap from the supplemental container, and wherein the supplementalcontainer holder is configured to automatically rotate in the other oneof the clockwise rotational direction and the counter-clockwiserotational direction while the second capping device engages thesupplemental container cap in order to install the supplementalcontainer cap onto the supplemental container.
 10. The system of claim8, wherein the first and second capping devices are offset from oneanother on the tool head such that, when the first capping device is ina position to grip and remove the sample container cap, the secondcapping device is in a position to grip and remove the supplementalcontainer cap without further rotational movement of the head tool. 11.The system of claim 7, further comprising a sample container held in thesample container holder and a supplemental container held in thesupplemental container holder.
 12. The system of claim 11, wherein thesupplemental container is an aliquot container, and wherein when thetool head and pipettor operatively cooperate to automatically cause thepipette tip engaging member to engage a pipette tip from the pipette tipdispenser, draw an aliquot of a sample from the sample container usingthe engaged pipette tip, and dispense the obtained sample aliquot intothe aliquot container, respectively.
 13. The system of claim 11, whereinthe supplemental container is a reagent container containing a reagent,and wherein when the tool head and pipettor operatively cooperate toautomatically cause the pipette tip engaging member to engage a pipettetip from the pipette tip dispenser, draw an aliquot of reagent from thereagent container using the engaged pipette tip, and dispense thereagent aliquot into the sample container, respectively.
 14. The systemof claim 1, wherein the analytic element positioner comprises a slidepositioner, the analytic element holder comprises a slide holder and theanalytic element comprises a slide.
 15. The system of claim 8, furthercomprising a controller for controlling operation of one or more of thetool head, pipettor, first capping device, second capping device, andanalytic element positioner, the system further comprising a userinterface operatively coupled with the controller and configured fordisplaying system status and/or inquires to a user, and for receivinguser inputs in response to the displayed system status and/or inquires.16. An automated system for processing a sample contained in a liquidsample container, the system comprising: a sample container holderconfigured for holding a sample container; an automated tool headconfigured to rotate about a first axis, and to translate along a secondaxis different than the first axis; a first capping device disposed at afirst circumferential position on the tool head such that the firstcapping device rotates with the tool head as the tool head is rotatedabout the first axis, the first capping device configured tocontrollably grip and release a cap of a sample container held in thesample container holder, wherein the tool head is configured toautomatically position the first capping device proximate the samplecontainer cap through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis, andwherein the first capping device operatively cooperates with the samplecontainer holder to remove or install the sample container cap; ananalytic element positioner having an analytic element holder configuredto releasably grip an analytic element; a specimen transfer devicecarried by the tool head at a second circumferential position on thetool head angularly spaced apart about the first axis from the firstcircumferential position such that the specimen transfer device rotateswith the tool head as the tool head is rotated about the first axis,wherein the tool head is configured to automatically position a workingend of the specimen transfer device to obtain a specimen from a samplecontainer held in the sample container holder, and to transfer theobtained specimen to an analytic element held by the analytic elementholder, respectively, through one or both of rotation of the tool headabout the first axis and translation of the tool head along the secondaxis, a pipette tin dispenser; a pipettor carried by the tool head, thepipettor having a pipette tip engaging member configured to releasablyengage pipette tips, wherein the tool head is configured toautomatically position the pipette tip engaging member proximate thepipette tip dispenser to allow the pipette tip engaging member to engagea pipette tip held by the pipette tip dispenser through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis, wherein the pipette tip dispenser ismounted on a pipette tip dispenser transporter configured to translatethe pipette tip dispenser relative to the tool head so that the pipettetip dispenser may be selectively translated to a location at which thetool head positions the pipette tip engaging member to engage a pipettetip from the pipette tip dispenser, and a pipette tip waste bin mountedon the pipette tip transporter, wherein the pipette tip dispensertransporter is configured to selectively translate the pipette tip wastebin to a location at which the tool head positions the pipette tipengaging member to disengage a pipette tip into the pipette tip wastebin, wherein the pipette tip waste bin is mounted on the pipette tiptransporter relative to the pipette tip dispenser such that, when thepipette tip waste bin is translated to the location at which the toolhead positions the pipette tip engaging member to disengage a pipettetip into the pipette tip waste bin, the pipette tip dispenser issimultaneously translated into the isolation chamber.
 17. An automatedsystem for processing a sample contained in a liquid sample container,the system comprising: a sample container holder configured for holdinga sample container; an automated tool head configured to rotate about afirst axis, and to translate along a second axis different than thefirst axis; a first capping device disposed at a first circumferentialposition on the tool head such that the first capping device rotateswith the tool head as the tool head is rotated about the first axis, thefirst capping device configured to controllably grip and release a capof a sample container held in the sample container holder, wherein thetool head is configured to automatically position the first cappingdevice proximate the sample container cap through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis, and wherein the first capping deviceoperatively cooperates with the sample container holder to remove orinstall the sample container cap; an analytic element positioner havingan analytic element holder configured to releasably grip an analyticelement; a specimen transfer device carried by the tool head at a secondcircumferential position on the tool head angularly spaced apart aboutthe first axis from the first circumferential position such that thespecimen transfer device rotates with the tool head as the tool head isrotated about the first axis, wherein the tool head is configured toautomatically position a working end of the specimen transfer device toobtain a specimen from a sample container held in the sample containerholder, and to transfer the obtained specimen to an analytic elementheld by the analytic element holder, respectively, through one or bothof rotation of the tool head about the first axis and translation of thetool head along the second axis; a pipette tip dispenser; a pipettorcarried by the tool head, the pipettor having a pipette tip engagingmember configured to releasably engage pipette tips, wherein the toolhead is configured to automatically position the pipette tip engagingmember proximate the pipette tip dispenser to allow the pipette tipengaging member to engage a pipette tip held by the pipette tipdispenser through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis; asupplemental container holder configured for holding a supplementalcontainer, wherein the tool head is configured to automatically positionthe pipette tip engaging member into a position in which a pipette tipengaged on the pipette tip engaging member is inserted into a samplecontainer held in the sample container holder, and into a position inwhich the engaged pipette tip is inserted into a supplemental containerheld in the supplemental container holder, respectively, through one orboth of rotation of the tool head about the first axis and translationof the tool head along the second axis; a sample container held in thesample container holder and a supplemental container held in thesupplemental container holder, wherein the supplemental container is analiquot container, and wherein when the tool head and pipettoroperatively cooperate to automatically cause the pipette tip engagingmember to engage a pipette tip from the pipette tip dispenser, draw analiquot of a sample from the sample container using the engaged pipettetip, and dispense the obtained sample aliquot into the aliquotcontainer, respectively; a reader positioned on the tool head andconfigured for reading sample container indicia located on the samplecontainer, and an aliquot container printer in communication with readerand configured for printing analytic element indicia corresponding tosample container indicia read by the reader onto an aliquot container.18. An automated system for processing a sample contained in a liquidsample container, the system comprising: a sample container holderconfigured for holding a sample container; an automated tool headconfigured to rotate about a first axis, and to translate along a secondaxis different than the first axis; a first capping device disposed at afirst circumferential position on the tool head such that the firstcapping device rotates with the tool head as the tool head is rotatedabout the first axis, and the first capping device configured tocontrollably grip and release a cap of a sample container held in thesample container holder, wherein the tool head is configured toautomatically position the first capping device proximate the samplecontainer cap through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis, andwherein the first capping device operatively cooperates with the samplecontainer holder to remove or install the sample container cap; a slidepositioner having a slide holder configured to releasably grip a slide;a specimen transfer device carried by the tool head at a secondcircumferential position of the tool head angularly space apart aboutthe first axis from the first circumferential position sch that thespecimen transfer device rotates with the tool head as the tool head isrotated about the first axis, wherein the tool head is configured toautomatically position a working end of the specimen transfer device toobtain a specimen from a sample container held in the sample containerholder, and to transfer the obtained specimen to a slide held by theslide holder, respectively, through one or both of rotation of the toolhead about the first axis and translation of the tool head along thesecond axis; a pipette tip dispenser; and a pipettor carried by the toolhead, the pipettor having a pipette tip engaging member configured toreleasably engage pipette tips, wherein the tool head is configured toautomatically position the pipette tip engaging member proximate thepipette tip dispenser to allow the pipette tip engaging member to engagea pipette tip held by the pipette tip dispenser through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis.
 19. The system of claim 18, furthercomprising a pipette tip dispenser transporter, wherein the pipette tipdispenser is mounted on a pipette tip dispenser transporter, the pipettetip dispenser transporter configured to translate the pipette tipdispenser relative to the tool head so that the pipette tip dispensermay be selectively translated to a location at which the tool headpositions the pipette tip engaging member to engage a pipette tip fromthe pipette tip dispenser, the system further comprising a pipette tipdispenser isolation chamber, wherein the pipette tip dispensertransporter is configured to selectively translate the pipette tipdispenser between the location at which the tool head positions thepipette tip engaging member to engage a pipette tip from the pipette tipdispenser and a second location within the isolation chamber.
 20. Thesystem of claim 19, further comprising a aliquot container holderconfigured for holding an aliquot container, wherein the tool head isconfigured to automatically position the pipette tip engaging memberinto a position in which a pipette tip engaged on the pipette tipengaging member is inserted into a sample container held in the samplecontainer holder, and into a position in which the engaged pipette tipis inserted into an aliquot container held in the aliquot containerholder, respectively, through one or both of rotation of the tool headabout the first axis and translation of the tool head along the secondaxis.
 21. The system of claim 20, further comprising a second cappingdevice disposed on the tool head and configured to controllably grip andrelease a cap of an aliquot container held in the aliquot containerholder, wherein the tool head is configured to automatically positionthe second capping device proximate the aliquot container cap throughone or both of rotation of the tool head about the first axis andtranslation of the tool head along the second axis, and wherein thesecond capping device operatively cooperates with the aliquot containerholder to remove or install the aliquot container cap.
 22. The system ofclaim 21, wherein the first and second capping devices are offset fromone another on the tool head such that, when the first capping device isin a position to grip and remove the sample container cap, the secondcapping device is in a position to grip and remove the aliquot containercap without further rotational movement of the head tool.
 23. The systemof claim 20, further comprising a sample container held in the samplecontainer holder and an aliquot container held in the aliquot containerholder, wherein when the tool head and pipettor operatively cooperate toautomatically cause the pipette tip engaging member to engage a pipettetip from the pipette tip dispenser, draw an aliquot of a sample from thesample container using the engaged pipette tip, and dispense theobtained sample aliquot into the aliquot container, respectively. 24.The system of claim 18, further comprising a slide loading platformlocated on a surface of the tool head, wherein the slide positioneroperatively cooperates with the tool head so that the slide holderautomatically engages and removes a slide placed on the slide loadingplatform, and wherein the slide positioner operatively cooperates withthe tool head to automatically position an engaged slide proximate theworking end of the specimen transfer device to transfer the specimenonto the engaged slide.
 25. An automated system for processing a samplecontained in a liquid sample container, the system comprising: a samplecontainer holder configured for holding a sample container; an automatedtool head configured to rotate about a first axis, and to translatealong a second axis different than the first axis; a first cappingdevice disposed on the tool head and configured to controllably grip andrelease a cap of a sample container held in the sample container holder,wherein the tool head is configured to automatically position the firstcapping device proximate the sample container cap through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis, and wherein the first capping deviceoperatively cooperates with the sample container holder to remove orinstall the sample container cap; a slide positioner having a slideholder configured to releasably grip a slide; a specimen transfer devicecarried by the tool head, wherein the tool head is configured toautomatically position a working end of the specimen transfer device toobtain a specimen from a sample container held in the sample containerholder, and to transfer the obtained specimen to a slide held by theslide holder, respectively, through one or both of rotation of the toolhead about the first axis and translation of the tool head along thesecond axis; a pipette tip dispenser; a pipettor carried by the toolhead, the pipettor having a pipette tip engaging member configured toreleasably engage pipette tips, wherein the tool head is configured toautomatically position the pipette tip engaging member proximate thepipette tip dispenser to allow the pipette tip engaging member to engagea pipette tip held by the pipette tip dispenser through one or both ofrotation of the tool head about the first axis and translation of thetool head along the second axis; a pipette tip dispenser transporter,wherein the pipette tip dispenser is mounted on a pipette tip dispensertransporter, the pipette tip dispenser transporter configured totranslate the pipette tip dispenser relative to the tool head so thatthe pipette tip dispenser may be selectively translated to a location atwhich the tool head positions the pipette tip engaging member to engagea pipette tip from the pipette tip dispenser, a pipette tip dispenserisolation chamber, wherein the pipette tip dispenser transporter isconfigured to selectively translate the pipette tip dispenser betweenthe location at which the tool head positions the pipette tip engagingmember to engage a pipette tip from the pipette tip dispenser and asecond location within the isolation chamber; a pipette tip waste binmounted on the pipette tip transporter, wherein the pipette tipdispenser transporter is configured to selectively translate the pipettetip waste bin to a location at which the tool head positions the pipettetip engaging member to disengage a pipette tip into the pipette tipwaste bin, and wherein the pipette tip waste bin is mounted on thepipette tip transporter relative to the pipette tip dispenser such that,when the pipette tip waste bin is translated to the location at whichthe tool head positions the pipette tip engaging member to disengage apipette tip into the pipette tip waste bin, the pipette tip dispenser issimultaneously translated into the isolation chamber.
 26. An automatedsystem for processing a sample contained in a liquid sample container,the system comprising: a sample container holder configured for holdinga sample container; an automated tool head configured to rotate about afirst axis, and to translate along a second axis different than thefirst axis; a first capping device disposed on the tool head andconfigured to controllably grip and release a cap of a sample containerheld in the sample container holder, wherein the tool head is configuredto automatically position the first capping device proximate the samplecontainer cap through one or both of rotation of the tool head about thefirst axis and translation of the tool head along the second axis, andwherein the first capping device operatively cooperates with the samplecontainer holder to remove or install the sample container cap; a slidepositioner having a slide holder configured to releasably grip a slide;a specimen transfer device carried by the tool head, wherein the toolhead is configured to automatically position a working end of thespecimen transfer device to obtain a specimen from a sample containerheld in the sample container holder, and to transfer the obtainedspecimen to a slide held by the slide holder, respectively, through oneor both of rotation of the tool head about the first axis andtranslation of the tool head along the second axis; a pipette tipdispenser; a pipettor carried by the tool head, the pipettor having apipette tip engaging member configured to releasably engage pipettetips, wherein the tool head is configured to automatically position thepipette tip engaging member proximate the pipette tip dispenser to allowthe pipette tip engaging member to engage a pipette tip held by thepipette tip dispenser through one or both of rotation of the tool headabout the first axis and translation of the tool head along the secondaxis; a reader positioned on the tool head and configured for readingsample container indicia located on a sample container, and a slideprinter in communication with reader and configured for printing slideindicia corresponding to sample container indicia read by the readeronto a slide.